Environmental research · 2025
Organochlorine pesticide use and mosaic loss of chromosome Y in a study of male farmers.
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Hurwitz Lauren M, Chang Vicky C, Beane Freeman Laura E, Machiela Mitchell J, Zhou Weiyin, Andreotti Gabriella, Parks Christine G, Sandler Dale P, Rothman Nathaniel, Berndt Sonja I, Hofmann Jonathan N, Koutros Stella
Аннотация
BACKGROUND: Organochlorine (OC) insecticides are a class of environmentally persistent chemicals linked to risk of several cancers, including non-Hodgkin lymphoma and prostate cancer. In vitro and animal studies suggest some OCs may be genotoxic, but evidence in humans is limited. Mosaic loss of the Y chromosome (mLOY) is a marker of genotoxicity and genomic instability that has been associated with certain cancers and may reflect intermediate effects of pesticide exposure. We examined associations between OC use and mLOY in circulating blood of male farmers.
METHODS: This investigation included 1653 male farmers from Iowa and North Carolina in the Biomarkers of Exposure and Effect in Agriculture study, a subcohort of the Agricultural Health Study. Ever use, total lifetime days, and intensity-weighted lifetime days of use of seven OCs (DDT, lindane, aldrin, dieldrin, chlordane, heptachlor, toxaphene) were derived from questionnaires. We detected mLOY using genotyping array intensity data in the pseudoautosomal regions of the sex chromosomes. Logistic regression was used to estimate associations between OC use and mLOY, adjusted for pre-specified confounders. Stratified analyses were performed by factors associated with mLOY (age, smoking status, obesity) and state of residence.
RESULTS: mLOY was detected in 357 farmers (21.6 %). We observed positive associations with mLOY for ever use of DDT (OR = 1.44 [95 % CI = 1.08-1.92]) and lindane (OR = 1.31 [0.99-1.73]). Associations were stronger among farmers without obesity (DDT: OR = 1.61 [1.12-2.33], p-interaction = 0.20; lindane: OR = 1.82 [1.28-2.59], p-interaction<0.01). For lindane, there was evidence of a positive exposure-response among farmers ≥70 years of age (p-trend = 0.03) and those without obesity (p-trend = 0.05). Other OCs were not consistently associated with mLOY.
CONCLUSIONS: Use of DDT and lindane was associated with mLOY, particularly in certain subgroups of farmers (e.g., non-obese or age ≥70 years). Our findings suggest that these pesticides could confer genotoxic effects and provide new mechanistic evidence for their associations with cancer risk.
METHODS: This investigation included 1653 male farmers from Iowa and North Carolina in the Biomarkers of Exposure and Effect in Agriculture study, a subcohort of the Agricultural Health Study. Ever use, total lifetime days, and intensity-weighted lifetime days of use of seven OCs (DDT, lindane, aldrin, dieldrin, chlordane, heptachlor, toxaphene) were derived from questionnaires. We detected mLOY using genotyping array intensity data in the pseudoautosomal regions of the sex chromosomes. Logistic regression was used to estimate associations between OC use and mLOY, adjusted for pre-specified confounders. Stratified analyses were performed by factors associated with mLOY (age, smoking status, obesity) and state of residence.
RESULTS: mLOY was detected in 357 farmers (21.6 %). We observed positive associations with mLOY for ever use of DDT (OR = 1.44 [95 % CI = 1.08-1.92]) and lindane (OR = 1.31 [0.99-1.73]). Associations were stronger among farmers without obesity (DDT: OR = 1.61 [1.12-2.33], p-interaction = 0.20; lindane: OR = 1.82 [1.28-2.59], p-interaction<0.01). For lindane, there was evidence of a positive exposure-response among farmers ≥70 years of age (p-trend = 0.03) and those without obesity (p-trend = 0.05). Other OCs were not consistently associated with mLOY.
CONCLUSIONS: Use of DDT and lindane was associated with mLOY, particularly in certain subgroups of farmers (e.g., non-obese or age ≥70 years). Our findings suggest that these pesticides could confer genotoxic effects and provide new mechanistic evidence for their associations with cancer risk.